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CCT007093 is a thienylidene cyclopentanone and shows a potent inhibition of PPM1D in the in vitro assay when using the recombinant phospho-P38 as a substrate. In cellular assay, CCT007093 shows specificity for MCF-7 cells over HeLa cells. It reduces 40% viability of the cells after 2 days. It is found that the cell death induced by CCT007093 is dependent on P38 kinase activity. CCT007093 mimics the effect of PPM1D RNAi in activating P38 kinase. It induces P38 phosphorylation at 4 h post-exposure in MCF-7 cells and the loss of viability can be rescued by SB203580, the specific P38 inhibitor [1].

References:

[1] Rayter S, Elliott R, Travers J, Rowlands MG, Richardson TB, Boxall K, Jones K, Linardopoulos S, Workman P, Aherne W, Lord CJ, Ashworth A. A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D. Oncogene. 2008 Feb 14;27(8):1036-44.

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